Flow cytometry and sorting has only recently been used to study biochemical events in mammalian cells. One of the major impediments to the application of flow cytometric methods to health problems has been the lack of interaction between professionals experienced in flow cytometry, and cell biologists or clinical scientists. Our grant also addresses this need by bringing together, in a common environment, biologists, clinicians, biophysicists, and engineers coordinated in a truly interdisciplinary effort. Our strategy is to develop new methodologies for flow cytometry which can be applied to basic research problems in immunology, cell biology, virology, and cytochemistry. We also regard development of increased data analysis capabilities as vital to the optimal use of these methodologies: only with the ability to quantify differences between overlapping subpopulations in a biological continuum can the basis of functional distinctions be understood. As possible clinical applications in these areas become evident, efforts to evaluate their usefulness can be undertaken. We have begun studies whose expressed goal is the enhancement of therapeutic ratio of chemotherapeutic drugs. In the field of autoimmune diseases we are developing a new diagnostic which may be useful to study autoantibodies not detectable by other means. In the area of fetal genetics we are attempting to enumerate and separate fetal cells from maternal circulation to provide risk free genetic analysis of the unborn fetus. All these clinical studies are made possible through collaborative efforts within this program project.